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1kits (Ebipipa 10) .
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▎ Enzimba ya Tirzepatid
Ensibuko: PubChem |
Omutendera: Tyr-{Aib}-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-{Aib}-Leu-Asp-Lys-Ile-Ala-Gln-{diaasidi-C20-gamm a-Glu-(AEEA)2-Lys}-Ala-Phe-Val-Gln-Trp-Leu-Ile-Ala-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 Ensengekera ya molekyu: C 225H 348N 48O68 Obuzito bwa molekyu: 4813 g/mol Ennamba ya CAS: 2023788-19-2 Ekitongole kya PubChem CID: 163285897 Ebigambo ebifaanagana: Zepbound; Mounjaro nga bwe |
▎ Okunoonyereza ku Tirzepatid
Kiki ekiva mu kunoonyereza ku Tirzepatid?
Tirzepatid ddagala lya polypeptide erikolebwa mu ngeri ey’ekikugu. Okunoonyereza n’okukulaakulanya kwayo kusibuka mu kutegeera okw’amaanyi ku buzibu obuliwo mu GLP-1 receptor agonists mu kujjanjaba ekika kya 2 metabolism n’omugejjo mu kiseera ekyo. Wadde nga GLP-1 receptor agonists ziraga nti zikola bulungi nnyo mu kufuga glucose mu musaayi n’okugejja, bannassaayansi baakizudde nti okukola kwazo ku GIP receptor kunafu nnyo, ekikoma ku bulung’amu bw’eddagala lino okutuuka ku ddaala eritali limu. N’olwekyo, ttiimu y’okunoonyereza n’okukulaakulanya yali yeewaddeyo okukola eddagala eppya eriyinza okukola GIPR ne GLP-1R omulundi gumu okusobola okutuuka ku kufuga kwa glucose mu musaayi n’okuddukanya obuzito mu ngeri enzijuvu era ennungi [1]..
Mu nkola y’okunoonyereza n’okukulaakulanya Tirzepatid, bannassaayansi baakola okunoonyereza okusookerwako okungi n’okugezesa mu malwaliro. Mu mutendera gw’okunoonyereza nga tekunnabaawo, okugezesa ku bisolo kwakozesebwa okwekenneenya obulungi eddagala lya Tirzepatid. Ebyavudde mu kunoonyereza bikakasizza obusobozi bwayo mu kufuga glucose mu musaayi n’okugejja, ne biteekawo omusingi gw’okugezesa okuddirira. Oluvannyuma, Tirzepatid yayingira mu mutendera gw’okugezesebwa mu malwaliro, omuli emitendera I, II, ne III. Omutendera I gwasinga kwekenneenya obukuumi, okugumiikiriza, n’obulungi bw’eddagala, era ebyavaamu byalaga obukuumi obulungi n’okugumiikiriza. Omutendera II gwayongera okunoonyereza ku bulungibwansi n’obukuumi bwa ddoozi ez’enjawulo mu balwadde abalina enkyukakyuka y’omubiri ey’ekika kya 2, nga basoose kusalawo ddoozi ezikola obulungi. Okugezesebwa kw’obujjanjabi okukulu okw’omutendera ogw’okusatu, gamba ng’okunoonyereza okwa SURPASS series, kwalimu abalwadde bangi abalina enkyukakyuka y’omubiri ey’ekika eky’okubiri. Ebivuddemu biraga nti Tirzepatid yali esinga nnyo GLP-1 receptor agonists eziriwo, nga Semaglutid, mu kukendeeza glucose mu musaayi n’obuzito, nga kiwa obujulizi obw’amaanyi ku nkola y’okutunda [1]..
Tirzepatid ye polypeptide erimu amino acids 39, era ensengekera yaayo ekyusiddwa okulongoosa obutebenkevu bwayo n’enkola y’eddagala. Ensengeka yaayo ey’enjawulo ey’ensengekera egisobozesa okugatta ebikolwa bya incretins bbiri, GIP ne GLP-1, mu molekyu emu, okukola ku bikwata obusimu ebikwatibwako mu kufuga glucose mu musaayi okuyita mu nkola bbiri. Okusingira ddala, ku ludda olumu, kikola ku kyenda okutumbula okufulumya insulini n’okuziyiza okufulumya glucagon okukendeeza ku glucose mu musaayi; ku ludda olulala, kikola ku busimu obw’omu makkati, okulwawo okufulumya amazzi mu lubuto, okwongera okukkuta, okukendeeza ku njagala y’okulya n’okulya emmere, n’okutuuka ku kukendeeza ku buzito. Enkola eno ey’emirundi ebiri ewa Tirzepatid enkizo ez’enjawulo mu kujjanjaba enkyukakyuka y’omubiri ey’ekika eky’okubiri n’omugejjo, n’ewa abalwadde eky’obujjanjabi ekisingako [1]..
Enkola ya Tirzepatid ekola ki?
Tirzepatid ekendeeza ku glucose mu musaayi ng’ayita mu nkola zino wammanga eziwera:
Okukola kwa GLP-1 Receptors: Tirzepatid yeekwata ku GLP-1 receptors ku pancreatic beta cells, nga ekoppa ekikolwa kya GLP-1 eky’obutonde. GLP-1 busimu obukolebwa ekyenda nga bukulu nnyo mu kukuuma glucose homeostasis. Kiyinza okutumbula okukola insulini, okufulumya, n’okutegeera glucose, n’okukendeeza ku kufulumya glucagon okutumbula okukkuta n’okuziyiza okwagala okulya. Mu balwadde abalina enkyukakyuka y’omubiri ey’ekika eky’okubiri, obutafulumya insulini emala oba okukendeeza ku buwulizi bw’obutoffaali ku insulini kivaako glucose mu musaayi okulinnya. Tirzepatid eyongera ku kufulumya insulini ng’ekola ku bikwata GLP-1, okulongoosa okufuga glucose mu musaayi. Mu kiseera kye kimu, okukola kw’ebikwata GLP-1 nakyo kisobola okuziyiza okufulumya glucagon, okwongera okukendeeza ku nsibuko za glucose mu musaayi n’okuyamba mu kufuga glucose mu musaayi [2]..
Okukola kwa GIP Receptors: Tirzepatid ekola ku GIP receptors, era okukola kwayo kuyinza okutumbula insulin sensitivity n’okufulumya. GIP receptors zisinga kubeera mu bitundu by’omubiri nga pancreatic beta cells. Oluvannyuma lw’okukola, okuyita mu kukyusa ekkubo ly’obubonero mu butoffaali, okufulumya insulini kweyongera, era okuddamu kw’obutoffaali ku insulini kwongera, okukendeeza ku glucose mu musaayi mu ngeri ennungi [2] . Kino dual receptor agonist effect kifuula Tirzepatid okukola obulungi okusinga single GLP-1 receptor agonists mu kutumbula okufulumya insulini n’okuziyiza okufulumya glucagon [2]..
Okulwawo okufulumya amazzi mu lubuto n’okwongera okukkuta: Tirzepatid esobola okulwawo okufulumya emmere mu lubuto, okuwangaaza obudde emmere gy’emala mu lubuto, okukendeeza ku sipiidi y’okunyiga ebiriisa, n’okuziyiza okulinnya ennyo kwa glucose mu musaayi oluvannyuma lw’okulya. Enkola yaayo ku kufulumya amazzi mu lubuto egeraageranyizibwa ku ya GLP-1 receptor agonists. Mu kiseera kye kimu, kikola ku busimu obw’omu makkati, okwongera okukkuta, okukendeeza ku njagala y’okulya n’okulya emmere, nga kino kituukira ddala ku kizibu ky’omugejjo ekitera okuwerekerwako abalwadde abalina enkyukakyuka y’omubiri ey’ekika eky’okubiri, ekiyamba okulongoosa obuziyiza bwa insulini n’embeera y’enkyukakyuka y’emmere okutwalira awamu [2]..
Okulongoosa Insulin Sensitivity ne Lipid Metabolism: Tirzepatid esobola okwongera ku mutindo gwa adiponectin, adipocytokine eyeekuusa ku insulin sensitivity, okuyamba okulongoosa insulin sensitivity, okusobozesa obutoffaali okutwala obulungi n’okukozesa glucose, n’okukendeeza glucose mu musaayi (Anonymous, 2023). Okugatta ku ekyo, era esobola okulongoosa enkola y’amasavu, nga erina ekiyinza okukuuma obulamu bw’emisuwa n’emitima. Kizuuliddwa nti kisobola okulongoosa puleesa, okukendeeza ku kolesterol wa LDL ne triglycerides [3]..
Ensibuko: PubMed [5] .
Emisomo ki egyekuusa ku nsonga eno?
Efficacy ku Weight Management mu balwadde abalina omugejjo ne Type 2 Metabolism
Okunoonyereza kungi kukakasizza nti Tirzepatid alina ekikolwa eky’amaanyi mu kugejja. Mu kunoonyereza kwa 'SURMOUNT-2', okugezesebwa kuno okw'omutendera ogw'okusatu, okugezesebwa okw'emirundi ebiri, okwa randomized, okwafugibwa placebo kwakolebwa mu nsi musanvu. Abantu abakulu (emyaka ≥ 18) nga balina BMI ya 27 kg/m² oba okusingawo ne HbA1 ya 7 - 10% zawandiisibwa era ne ziweebwa mu ngeri ey’ekifuulannenge okufuna empiso ya Tirzepatid (10 mg oba 15 mg) oba placebo omulundi gumu buli wiiki wansi w’olususu okumala wiiki 72. Ebivuddemu biraga nti mu wiiki 72, ebitundu by’okugejja mu bibinja bya Tirzepatid 10 mg ne 15 mg byali -12.8% ne -14.7%, bw’ogeraageranya ne -3.2% mu kibinja kya placebo. Enjawulo mu bujjanjabi ebalirirwamu eza Tirzepatid 10 mg ne 15 mg bw’ogeraageranya n’ekirungo kya placebo zaali -9.6 ku buli 100 ne -11.6 ku buli 100, nga zino zaali za maanyi mu bibalo (p < 0.0001). Okugatta ku ekyo, abalwadde bangi abafuna obujjanjabi bwa Tirzepatid baatuuka ku kigero ky’okugejja ebitundu 5% oba okusingawo (79 - 83% vs 32%) (Garvey WT, 2023). Mu kunoonyereza kuno, obuzito obw’omusingi obwa wakati bwali kkiro 100.7, BMI yali kkiro 36.1/m², ate HbA1 yali 8.02%. Oluvannyuma lwa wiiki 72 ng’ajjanjabwa, Tirzepatid teyakoma ku kukendeeza nnyo ku buzito bw’omubiri naye era yalina akakwate akalungi ku kufuga glucose mu musaayi [4]..
Okulongoosa mu bulwadde bwa sukaali obw’obusimu
Okunoonyereza kulaga nti GLP1-RAs zisobola okukendeeza ku bulabe bw’okusannyalala mu balwadde abalina enkyukakyuka y’omubiri ey’ekika eky’okubiri nga zitereeza okujjukira, okuyiga, n’okuvvuunuka obuzibu mu kutegeera. Nga GIP-RA/GLP-1RA ey’emirundi ebiri, mu layini y’obutoffaali bwa neuroblastoma (SHSY5Y), okunoonyereza kuzudde nti Tirzepatid erina akakwate ku bubonero bw’okukula kw’obusimu (CREB ne BDNF), apoptosis (BAX/Bcl2 ratio), okwawukana (pAkt, MAP2, GAP43, ne AGBL4), n’okuziyiza insulini (GLUT1, GLUT4, GLUT3, ne SORBS1). Ebivuddemu biggumiza omulimu gwa Tirzepatid mu kukola ekkubo lya pAkt/CREB/BDNF ne downstream signaling cascades n’obulungi bwayo obw’okukuuma obusimu, ekiraga nti esobola okuziyiza ebikosa ebikwatagana ne hyperglycemia n’okuziyiza insulini ku mutendera gw’obusimu. N’olwekyo, Tirzepatid esobola okulongoosa okuvunda kw’obusimu obuva ku sukaali omungi n’okuvvuunuka okuziyiza insulini y’obusimu, okuwa amagezi amapya ku kulongoosa obulwadde bw’obusimu obukwatagana n’okukyusakyusa emmere [5]..
Enkulaakulana y’okunoonyereza mu kujjanjaba enkyukakyuka y’omubiri ey’ekika kya 2
Ng’ekika ekipya eky’eddagala erikendeeza sukaali mu musaayi, Tirzepatid efuuse eddagala erisoose erya dual GIP/GLP-1R agonist eryakkirizibwa okujjanjaba enkyukakyuka mu mubiri mu Amerika. Okugezesebwa okuwerako okw’amaanyi kukakasizza nti ekola nnyo okukendeeza ku glucose mu musaayi n’okugejja, era erina obusobozi mu kukuuma emisuwa gy’omutima. Endowooza ya synthetic peptides egguddewo ebintu bingi ebitamanyiddwa ku Tirzepatid. Okugezesebwa okugenda mu maaso (NCT04166773) n’obujulizi biraga nti ddagala erisuubiza mu by’obulwadde bw’ekibumba obutali bwa masavu (NAFLD), okukuuma ekibumba n’obusimu [6] (Ma Z, 2023).
Enkola ya Tirzepatid ey’ekiseera ekiwanvu ku bulamu bw’emisuwa n’emisuwa
Tirzepatid eyinza okukendeeza ku bulabe bw’endwadde z’emisuwa ng’etumbula okugejja. Okunoonyereza kwekenneenya enkola ya Tirzepatid ku mugejjo n’endwadde z’emisuwa mu bantu abakulu mu Amerika [7] . Okunoonyereza kuzudde nti mu bantu abakulu mu Amerika abalina ebisaanyizo okuweebwa obujjanjabi bwa Tirzepatid, oluvannyuma lw’okujjanjabwa n’eddagala lya Tirzepatid 15 mg, abantu abakulu ababalirirwamu 70.6% ne 56.7% baafiirwa ≥ 15% ne ≥ 20% ku buzito bw’omubiri gwabwe, ekitegeeza nti omuwendo gw’abantu abagejjulukuka gwakendeera ebitundu 58.8%. Mu abo abatalina bulwadde bw'emisuwa, obulabe obubalirirwamu obw'emyaka 10 obw'endwadde z'emisuwa bwakendeera okuva ku 10.1% 'nga tebannaba kujjanjabwa' okutuuka ku 7.7% 'oluvannyuma lw'okujjanjabwa', nga obulabe obw'enkomeredde bukendedde ebitundu 2.4% n'okukendeeza ku bulabe obw'enjawulo obwa 23.6%, ne kiziyiza ebikolwa by'endwadde z'emisuwa obukadde 2.
Mu kumaliriza, Tirzepatid kika kipya kya dual agonist of GIP ne GLP-1 receptors, nga kino kya makulu nnyo mu kujjanjaba ekika kya 2 metabolism n’omugejjo. Kiyinza okutumbula obulungi okufulumya insulini, okuziyiza okufulumya glucagon, okutereeza obulungi glucose mu musaayi, okukendeeza ku bulabe bw’ebizibu, okulongoosa enkola y’obutoffaali bwa beta obw’olubuto, okulwawo okukula kw’enkyukakyuka mu mubiri, era kirina ekikolwa eky’okukuuma omutima. Mu kujjanjaba omugejjo, kisobola bulungi okukendeeza ku mmere gye balya, okukendeeza ku njagala y’okulya, okwongera okukkuta, okuyamba abalwadde abagejjulukuka okugejja, n’okukendeeza ku bulabe bw’ebizibu ebiva ku mugejjo. Era asobola okulongoosa obuziyiza bwa insulini n’okukyusakyusa amasavu. Okugatta ku ekyo, eraga obusobozi mu kujjanjaba endwadde ezikwatagana n’enkyukakyuka y’emmere ezitali za bulijjo nga obulwadde bw’ekibumba obutali bwa mwenge, obulwadde bw’okusannyalala mu tulo, n’okulemererwa kw’omutima, era mu kiseera kye kimu esobola okulongoosa ebiraga enkyukakyuka y’emmere eziwera, ne kiwa enteekateeka y’obujjanjabi enzijuvu. Enkola yaayo ey’okukuba empiso omulundi gumu buli wiiki nnyangu okukozesa era esobola okulongoosa abalwadde okugoberera obujjanjabi. Nga efuga bulungi glucose mu musaayi n’obuzito n’okukendeeza ku bulabe bw’ebizibu, esobola okulongoosa ennyo embeera y’omubiri gw’abalwadde, okutumbula obusobozi bwabwe obw’okukola emirimu gya buli lunaku n’omutindo gw’obulamu, okwongera obwesige bwabwe mu kufuga endwadde, okukendeeza ku buzito bw’eby’omwoyo, n’okulongoosa embeera yaabwe ey’okukyusakyusa mu mbeera z’abantu.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Dr. William T. Garvey mukenkufu era munoonyereza ow’ekitiibwa alina akakwate n’amatendekero ag’ekitiibwa agawerako, omuli Yunivasite y’e Alabama e Birmingham, Yunivasite ya Aston, ne Birmingham Veterans Affairs Medical Center. Obuyigirize bwe n’obumanyirivu bwe mu by’emikono bikwata ku bintu bingi mu by’obusawo ne ssaayansi. Dr. Garvey akoze kinene mu bitundu by’eby’omubiri n’okukyusakyusa ebiriisa, endya n’emmere, biochemistry ne molecular biology, wamu n’obusawo obw’enjawulo n’obw’omunda, ng’essira aliteeka nnyo ku nkola y’emisuwa n’omutima. Omulimu gwe gubadde gumanyiddwa nnyo era ne guweebwa ekitiibwa, naddala okulondebwa ng’Omunoonyereza Amanyiddwa ennyo mu mutendera gwa Cross-Field mu mwaka gwombi ogwa 2023 ne 2024, ekiraga enkosa ennene n’enkola y’okunoonyereza kwe ku kibiina kya ssaayansi ekigazi.
Dr. Garvey by’ayagala mu kunoonyereza n’obukugu bituuka ku bintu eby’enjawulo ebikwata ku ndwadde z’enkyukakyuka mu mubiri n’enzirukanya yazo. Abadde yeenyigira nnyo mu kusoma ku nkyukakyuka y’emmere, omugejjo, n’ebizibu ebikwatagana nabyo, ng’agenderera okuzuula enkola empya ez’obujjanjabi n’okulongoosa ebiva mu balwadde. Omulimu gwe guzingiramu okunoonyereza kwa ssaayansi okusookerwako, okugezesa mu bujjanjabi, n’okunoonyereza ku kuvvuunula, okuziba ekituli wakati w’ebizuuliddwa mu laboratory n’okukozesebwa mu by’obujjanjabi mu nsi entuufu. Okuyita mu kunoonyereza kwe okw’amaanyi, Dr. Garvey ayambye okutegeera ennyo enkola ezisibukamu obuzibu mu nkyukakyuka y’emmere era ayambye okukola ebiragiro by’obujjanjabi n’enkola z’obujjanjabi mu by’endocrinology n’enkyukakyuka y’emmere. Dr. William T. Garvey awandiikiddwa mu kiwandiiko ekijuliziddwa [4 ].
